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Title: Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating b-cell lymphoma 2 and inducing cell cycle arrest
Authors: Pannaree Piromkraipak
Tipparat Parakaw
Suttinee Phuagkhaopong
Sirada Srihirun
Sukumal Chongthammakun
Kulathida Chaithirayanon
Pornpun Vivithanaporn
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2018
Citation: Canadian Journal of Physiology and Pharmacology. Vol.96, No.8 (2018), 798-806
Abstract: © 2018, Canadian Science Publishing. All rights reserved. Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion, and migration. Montelukast and zafirlukast, 2 widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and migration of glioblastoma cell lines. Montelukast induces apoptosis and inhibits cell proliferation of various cancer cells. Herein, apoptotic and antiproliferative effects of montelukast and zafirlukast were investigated in 2 glioblastoma cell lines, A172 and U-87 MG. Both LTRAs induced apoptosis and inhibited cell proliferation of glioblastoma cells in a concentration-dependent manner. Montelukast was more cytotoxic and induced higher levels of apoptosis than zafirlukast in A172 cells, but not in U-87 MG cells. Both drugs decreased expression of B-cell lymphoma 2 (Bcl-2) protein without affecting Bcl-2-associated X (Bax) levels. LTRAs also reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, zafirlukast showed a greater antiproliferative effect than montelukast and induced G0/G1 cell cycle arrest by upregulating p53 and p21 expression. These results suggested the therapeutic potential of LTRAs in glioblastoma.
ISSN: 12057541
Appears in Collections:Scopus 2018

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